..5 kg/m(2), 2.6% [95% CI -1.4 to 6.6], P = 0.20), age categories did not. The addition of the gene score to a phenotypic risk model leads to a potentially clinically important improvement in discrimination of incident T2D. ..

Genetic and environmental determinants of plasma high density lipoprotein cholesterol and apolipoprotein AI concentrations in healthy middle-aged men

..Considering gene-environment interaction has the potential not only for improving our understanding of the pathophysiology of the disease, but also in the development and targeting of specific therapies...

..007). In conclusion, hypertensive LPL X447 carriers have increased risk of LVH and CHD, suggesting that altered FA delivery constitutes a mechanism through which LVH and CHD are associated in hypertensive subjects...

Philippa J TalmudCentre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College London Medical School, 5 University Street, London WC1E 6JF, UKAtherosclerosis 194:287-92. 2007

..The insight these truncated protein give to the structure-function relationship of apoAV is explored and the relative importance of plasma and liver apoAV discussed...

..006 mm) in 19SS men (P = 0.08). There was no effect of genotype on the response of these parameters to gemfibrozil treatment. These results shed new light on the role of APOA5 variants in TG metabolism and coronary heart disease risk...

How to identify gene-environment interactions in a multifactorial disease: CHD as an example

..Hormone sensitive lipase (HSL) plays a central role in free fatty acid homeostasis in adipose tissue and in pancreatic beta-cells, where it contributes to the control of insulin secretion by generating long-chain fatty acids...

The significant increase in cardiovascular disease risk in APOEepsilon4 carriers is evident only in men who smoke: potential relationship between reduced antioxidant status and ApoE4

Philippa J TalmudDivision of Cardiovascular Genetics, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, United KingdomJ Biol Chem 280:28215-20. 2005

..Alternatively, the effect on TG levels may reflect the strong linkage disequilibrium with the functional APOC3 SNPs...

Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study

P J TalmudDepartment of Medicine, Royal Free and University College London Medical School, UKCurr Opin Lipidol 11:31-6. 2000

..In addition, the effect of nutrients can be directly evaluated at the level of gene expression, and reports of in-vitro studies of control of fatty acid and triglycerides synthesis are discussed in the present review...

Linkage of the cholesteryl ester transfer protein (CETP) gene to LDL particle size: use of a novel tetranucleotide repeat within the CETP promoter

..The 5' sequence shows 57-59% homology with the mouse promoter with higher homology at potential regulatory motifs. Thus, the 1.7 kb of 5' sequences is well conserved and may play a part in the regulation of HSL gene expression...

David M FlavellCentre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College of London Medical School, London, UKCirculation 105:1440-5. 2002

..Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD)...

Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women

..17) and haplotype frequencies differed markedly in this group. These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D...

..90+/-0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV...

The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes

Birgit DorfmeisterCentre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF, UKBiochim Biophys Acta 1772:355-63. 2007

..However, comparison between EWs with T2D and healthy EWs suggest APOC3 1100C>T is associated with increased risk of diabetes probably through mechanisms other than direct effects on TG...

Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges

..Our results strongly support the role of APOA5 in determining plasma TG levels in an age-independent manner and highlight the importance of the APOC3/A4/A5 gene cluster in both TG and metabolic homeostasis...

..In conclusion, PLA2G5 tSNP haplotypes demonstrate an association with total and LDL cholesterol and oxLDL/LDL, not seen with PLA2G2A, thus confirming distinct functional roles for these two sPLA2s...

..The strong impact of PLA2G2A haplotypic variation on sPLA(2)IIa levels will help clarify the causality of this association...

Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: lipoprotein lipase genotype and plasma triglycerides as an exemplar

Gie Ken-DrorCentre for Cardiovascular Genetics, BHF Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London, United KingdomMol Med 16:389-99. 2010

..While the common APOE polymorphism explains the majority of the locus genetic determinants of plasma lipid levels, additional SNPs in the APOC1/C2 region may contribute to CHD risk, but these effects require confirmation...

The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA52, and their paradoxical association with plasma triglyceride but not plasma apoAV levels

Reecha SofatCentre for Clinical Pharmacology, Department of Medicine, University College London, London, United KingdomCirculation 121:52-62. 2010

..We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target...

Variable effects of the APOC3-482C > T variant on insulin, glucose and triglyceride concentrations in different ethnic groups

..Thus, despite a modest effect of the INS VNTR alone, the influence of this variant on insulin sensitivity was modified by gene:environment and gene:gene interactions, illustrating the biological complexity of insulin resistance...

Genetic variation in complement factor H and risk of coronary heart disease: eight new studies and a meta-analysis of around 48,000 individuals

..0002) on AUC TG and APOC3 -482C>T on plasma apoE levels (P=0.0012). Thus, in these healthy young men, variation in USF1 was the influencing feature of both glucose and lipid homeostasis showing case-control heterogeneity...

Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe

A M AbuzeidDivision of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University St, London WC1E 6JJ, UKAtherosclerosis 168:283-8. 2003

....

Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals

Tauseef A KhanFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UKInt J Epidemiol 42:475-92. 2013

..We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk...

..Copy number variants (CNVs) are a major form of genomic variation, which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited...

..51+/-1.17%) in percentage lean mass, compared to AV (1.64+/-0.38%) and AA (1.10+/-0.24%) recruits (p=0.02). The association of this genotype with changes in body composition after training suggests a novel role for Lp-PLA2...

Family history is a coronary heart disease risk factor in the Second Northwick Park Heart Study

..001. These data demonstrate the complex interaction between genetic and environmental factors in determining CHD risk, and suggest that the causes of the familial clustering of CHD remain largely unexplained...

Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding

..The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible...

The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease

Wai Man R WongCentre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF, United KingdomJ Lipid Res 45:1565-71. 2004

..This study offers direct support for an antioxidant capacity of apoA-IV, thus providing some explanation for the antiatherogenic role of apoA-IV and the higher CVD risk in S347 homozygotes...

Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study

..Our findings show that DDAH1 modulates plasma asymmetric dimethylarginine and contributes to the decline in renal function. However, it appears that increases in circulating methylarginine did not mediate progressive kidney injury...

Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation

Wai Man R WongCentre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, UKAtherosclerosis 192:266-74. 2007

..The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress...

Variants in the APOC3 promoter insulin responsive element modulate insulin secretion and lipids in middle-aged men

..The finding of an elevated 30-min NEFA may be an important mechanistic link between triglyceride-rich lipoprotein (TRL) metabolism and glucose homeostasis...

Blood pressure loci identified with a gene-centric array

Toby JohnsonClinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UKAm J Hum Genet 89:688-700. 2011

....

Genetic variation in alcohol dehydrogenase 1C and the beneficial effect of alcohol intake on coronary heart disease risk in the Second Northwick Park Heart Study

Jenan YounisDivision of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, UKAtherosclerosis 180:225-32. 2005

..These findings confirm that the cardiovascular benefit of modest alcohol consumption. ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported...

Rachel M FisherDepartment of Medicine, Royal Free and University College Medical School, Rayne Institute, 5 University Street, London WC1E 6JJ, UKAtherosclerosis 166:243-51. 2003

..Thus once on the cell surface, LPL-N9 enhances bridging, as assessed both by LDL binding and internalisation, and monocyte adhesion. This augmented LPL-N9 bridging provides a mechanism for the reported increased CAD risk in N9 carriers...

F MaillyDepartment of Medicine, University College London Medical School, UKHum Mutat 10:465-73. 1997

..Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence...

Aroon D HingoraniDivision of Population Sciences, Department of Epidemiology and Public Health, University College London, London, UKClin Chem 55:239-55. 2009

..The research has encompassed observational and genetic epidemiology, basic science studies with cells and tissues, experiments with animal models and humans, and randomized trials (although not of specific CRP-lowering therapies as yet)...

..Carriers of N9 appear to be especially vulnerable to the adverse effects of cigarette smoking on IHD risk, but this susceptibility is unrelated to the influence of this variant on plasma TG levels...

The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study. Lopid Coronary Angiography Trial

..Greater knowledge of the underlying mechanisms of these variations within the LPL gene may be of considerable importance in understanding genetic predisposition to atherosclerosis and heart disease...

Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr

H LiuCardiovascular Genetics Division, Department of Medicine, Royal Free and University College London Medical School, London WC1E 6JJ, UKJ Lipid Res 41:1760-71. 2000

....

Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS)

..The importance of the apolipoprotein A5 (APOA5) gene in determining plasma triglyceride (TG) levels has been demonstrated in transgenic and knockout mice and confirmed by human association studies in different ethnic groups...

Evidence of admixture from haplotyping in an epidemiological study of UK Caucasian males: implications for association analyses

Xiao He ChenHuman Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, EnglandHum Hered 57:142-55. 2004